Exacerbation of human immunodeficiency virus infection in promonocytic cells by bacterial immunomodulators

Article Abstract:

Not only can monocytes, a type of white blood cell, be infected with the AIDS virus, but there is some suggestion that these cells may provide the reservoir which facilitates persistent infection with HIV. It may be important, then, to learn more about the characteristics of infected monocytes and related cells. Since monocytes, as well as many other leukocytes, respond to stimulation with compounds produced by bacteria, the effect of such stimulation on HIV-infected cells was investigated. These stimulating compounds, collectively called bacterial immunomodulators, include substances such as trehalose dimycolate and monophosphoryl lipid A. A synthetic substance, muramyl dipeptide, is often included among the bacterial immunomodulators, as it represents the attempt to identify the minimal portion of the modulators necessary to elicit the cellular response. Using cell line U937, which behaves like precursors of normal monocytes, it was found that stimulation of infected cells with the immunomodulators produced a transient depression of synthesis of viral proteins followed by a rapid increase. This increase in virus production was accompanied by an increase in the production of interleukin-1. These results suggest that great caution must be taken in efforts to therapeutically improve immune system function of patients with AIDS. Since the stimulation of immune cells has, in this case, been shown to result in an increase in virus production, efforts to enhance immune function in AIDS patients may, in fact, achieve the opposite of the desired result. (Consumer Summary produced by Reliance Medical Information, Inc.)

Drug therapy, Endotoxins

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HIV-1 neutralizing antibodies in urine from seropositive individuals

Article Abstract:

Antibodies are the front-line protection against many viral infections. But it is not sufficient only to have antibodies against a virus, the antibodies must also be neutralizing antibodies. In other words, the antibodies must not only bind to the virus, they must inhibit the ability of the virus to infect cells. Antibodies to the AIDS virus are found in virtually all patients, but in only a minority of cases do the antibodies have the capability of neutralizing the AIDS virus. The precise mechanism of this neutralizing ability is not yet known, nor is the relationship these antibodies have to the development of the disease. Research has now identified a surprising, and apparently unprecedented facet of the antibody response in AIDS. In a study of 56 HIV-infected patients, 19 were found to have high titers of neutralizing antibodies to HIV in their urine. Surprisingly, in 11 patients, neutralizing antibodies could be found in the urine, despite the apparent absence of neutralizing antibodies in the patients' serum. Antibody molecules are sufficiently large that they are generally retained by the kidney and do not appear in the urine, at least in their native form. The loss of neutralizing antibodies in the urine of some patients may result from a mechanism not yet described in the medical literature. If further research confirms this unusual loss of neutralizing antibodies, it may have important implications for the development and maintenance of immunity against the AIDS virus. (Consumer Summary produced by Reliance Medical Information, Inc.)

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Immune response to HIV-1 gag antigens induced by recombinant adenovirus vectors in mice and rhesus macaque monkeys

Article Abstract:

The goal of much AIDS research has been to develop a vaccine that will stimulate the immune system to make antibodies so that infection with the human immunodeficiency virus type-1 (HIV-1) can be prevented. A class of human viruses, known as the adenoviruses, can be genetically altered to express the proteins of HIV-1. This was done with two proteins gag (p55) and CA (capsid antigen; p24). These viruses were injected into mice to test whether the proteins would be expressed by living animals and to see whether the proteins would provoke an immune reaction. Antibodies to the CA protein were expressed earlier and in larger quantities than the p55 protein. The mutant viruses expressing the CA protein were injected into primates, rhesus monkeys. Two out of four monkeys that were immunized developed antibodies against the CA protein. No adverse reactions were seen in the monkeys after injection. These mutant viruses expressing HIV-1 proteins can be further developed for use in humans as possible vaccines to prevent or inhibit infection with HIV-1. (Consumer Summary produced by Reliance Medical Information, Inc.)

Prevention, Synthetic vaccines

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